We have located links that may give you full text access.
Efficacy and Safety of Ivabradine Once-Daily Prolonged-Release versus Twice-Daily Immediate-Release Formulation in Patients with Stable Chronic Heart Failure with Systolic Dysfunction: A Randomized, Double-Blind, Phase 3 Non-Inferiority (PROFICIENT) Study.
Cardiology and Therapy 2020 October 2
INTRODUCTION: Dosing frequency is an important factor influencing medication compliance in patients with heart failure (HF), which in turn is imperative in achieving the desired therapeutic outcome. Here we assessed the efficacy and safety of ivabradine prolonged-release (PR) once-daily (test) vs. ivabradine immediate-release (IR) twice-daily (reference) formulations in patients with stable chronic HF with systolic dysfunction.
METHODS: Patients with sinus rhythm and heart rate (HR) ≥ 50 bpm, left ventricular ejection fraction ≤ 40% (HF with reduced ejection fraction), on guideline-based standard care, receiving a stable dose of ivabradine IR 5/7.5 mg twice daily for ≥ 1 month were enrolled in this randomized, double-blind, phase 3 non-inferiority study. Patients were randomly assigned 1:1 to ivabradine PR (10 mg/15 mg) based on the ivabradine IR dosage or continued ivabradine IR (5 mg/7.5 mg). The primary endpoint was change in resting ECG HR from baseline to the end of 3 months, assessed by 12-lead ECG. Safety assessments and 24-h Holter HR monitoring (in a subgroup of patients) were also performed. Non-inferiority was concluded if the upper limit of the 95% CI of the difference between the test and reference was less than the margin of 6.5 bpm in the per-protocol set.
RESULTS: A total of 169 out of 180 randomized patients (93.9%) completed the study (PR = 84; IR = 85). The least-square mean (standard error [SE]) for change in HR from baseline to 3 months was 0.76 (1.188; 95% CI -1.59:3.11) in ivabradine PR vs. ivabradine IR, which was within the pre-specified margin of 6.5 bpm, confirming the non-inferiority of ivabradine PR. The change from baseline to 3 months was comparable between the treatment groups for 24-h Holter ECG monitoring (p = 0.3701), mean HR awake (p = 0.3423), and mean HR asleep (p = 0.1501). Thirty-nine treatment-emergent adverse events (TEAEs) were reported; the majority in both groups were of mild or moderate severity and were subsequently resolved. Seven serious adverse events were reported (ivabradine PR = 2; ivabradine IR = 5), of which one was fatal (ivabradine IR group). The bradycardia events reported were comparable between groups.
CONCLUSION: Ivabradine PR was found to be non-inferior to ivabradine IR in the management of patients with stable CHF, with a comparable safety profile. Once-daily ivabradine PR effectively maintained the HR in patients shifted from the ivabradine IR twice-daily regimen, and thus may aid in improving treatment compliance.
TRIAL REGISTRATION: CTRI/2018/04/013464 (Trial Registered Prospectively on 24/04/2018).
METHODS: Patients with sinus rhythm and heart rate (HR) ≥ 50 bpm, left ventricular ejection fraction ≤ 40% (HF with reduced ejection fraction), on guideline-based standard care, receiving a stable dose of ivabradine IR 5/7.5 mg twice daily for ≥ 1 month were enrolled in this randomized, double-blind, phase 3 non-inferiority study. Patients were randomly assigned 1:1 to ivabradine PR (10 mg/15 mg) based on the ivabradine IR dosage or continued ivabradine IR (5 mg/7.5 mg). The primary endpoint was change in resting ECG HR from baseline to the end of 3 months, assessed by 12-lead ECG. Safety assessments and 24-h Holter HR monitoring (in a subgroup of patients) were also performed. Non-inferiority was concluded if the upper limit of the 95% CI of the difference between the test and reference was less than the margin of 6.5 bpm in the per-protocol set.
RESULTS: A total of 169 out of 180 randomized patients (93.9%) completed the study (PR = 84; IR = 85). The least-square mean (standard error [SE]) for change in HR from baseline to 3 months was 0.76 (1.188; 95% CI -1.59:3.11) in ivabradine PR vs. ivabradine IR, which was within the pre-specified margin of 6.5 bpm, confirming the non-inferiority of ivabradine PR. The change from baseline to 3 months was comparable between the treatment groups for 24-h Holter ECG monitoring (p = 0.3701), mean HR awake (p = 0.3423), and mean HR asleep (p = 0.1501). Thirty-nine treatment-emergent adverse events (TEAEs) were reported; the majority in both groups were of mild or moderate severity and were subsequently resolved. Seven serious adverse events were reported (ivabradine PR = 2; ivabradine IR = 5), of which one was fatal (ivabradine IR group). The bradycardia events reported were comparable between groups.
CONCLUSION: Ivabradine PR was found to be non-inferior to ivabradine IR in the management of patients with stable CHF, with a comparable safety profile. Once-daily ivabradine PR effectively maintained the HR in patients shifted from the ivabradine IR twice-daily regimen, and thus may aid in improving treatment compliance.
TRIAL REGISTRATION: CTRI/2018/04/013464 (Trial Registered Prospectively on 24/04/2018).
Full text links
Related Resources
Trending Papers
Executive Summary: State-of-the-Art Review: Unintended Consequences: Risk of Opportunistic Infections Associated with Long-term Glucocorticoid Therapies in Adults.Clinical Infectious Diseases 2024 April 11
Autoimmune Hemolytic Anemias: Classifications, Pathophysiology, Diagnoses and Management.International Journal of Molecular Sciences 2024 April 13
Clinical practice guidelines on the management of status epilepticus in adults: A systematic review.Epilepsia 2024 April 13
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app
All material on this website is protected by copyright, Copyright © 1994-2024 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.
By using this service, you agree to our terms of use and privacy policy.
Your Privacy Choices
You can now claim free CME credits for this literature searchClaim now
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app